QSAR Model of Indeno[1,2-b]indole Derivatives and Identification of N-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-b]furan-3-carboxamide as a Potent CK2 Inhibitor

Haidar, Samer; Marminon, Christelle; Aichele, Dagmar; Nacereddine, Abdelhamid; Zeinyeh, Waël; Bouzina, Abdeslem; Berredjem, Malika; Ettouati, Laurent; Bouaziz, Zouhair; Borgne, Marc Le; Jose, Joachim

doi:10.3390/molecules25010097

Cited by 12 publications

(11 citation statements)

References 40 publications

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“…Furan-3-carboxamide derivatives are basic units of many natural products. [65][66][67] They possess diverse biological applications like usage in treatment of antiviral infections and hyperproliferative diseases. 68 In 2014, Yong Rok Lee et al reported a regioselective synthesis of furan-3-carboxamide derivatives using cascade formal [3+2] cycloaddition (Scheme 21).…”

Section: Account Synlettmentioning

confidence: 99%

Recent Advances in [3+2]-Cycloaddition-Enabled Cascade Reactions: Application to Synthesize Complex Organic Frameworks

Erande¹,

Shivam²,

Chavan³

et al. 2022

Synlett

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Many natural products and biologically important complex organic scaffolds have convoluted structures around their core skeleton. Interestingly, with just changing the outskirts, the core reflects new and unique degrees of various physical and chemical properties. A very common but intriguing core is a five-membered ring horning heaps of organic molecules crafts. The power of [3+2] cycloaddition reactions to generate five-membered ring systems allocate chemists to envision synthetic procedures of wonder molecules and if it is facilitating a cascade sequence, then the end product will imbibe significant level of complexity having applications in medicinal and pharmaceutical fields. This Account highlights the broad interest in assembling recent advances in cascade reactions involving [3+2] cycloaddition as the power tool in order to conceive breakthrough organic architectures reported in the last ten years. We foresee that our comprehensive collection of astonishing [3+2] cycloaddition enabled cascades will provide valuable insights to polycyclic molecular construction and perseverant approach towards nonconventional synthetic procedures to the organic community.1 Introduction2 Synthesis of Oxindoles Skeleton3 Synthesis of Oxazoles Skeleton4 Synthesis of Oxadiazoles Skeleton5 Synthesis of Nitrogen-Containing Heterocycles6 Synthesis via Formal [3+2] Cycloaddition7 Synthesis of Miscellaneous Scaffolds8 Conclusion

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Section: Account Synlettmentioning

confidence: 99%

Recent Advances in [3+2]-Cycloaddition-Enabled Cascade Reactions: Application to Synthesize Complex Organic Frameworks

Erande¹,

Shivam²,

Chavan³

et al. 2022

Synlett

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“…Naphthofurans fused or coupled with oxygen and nitrogen heterocycles do not occur in nature. Even synthetic naphthofurans coupled or fused with oxygen and nitrogen heterocycle are not reported so far, except for some reports of such compounds from this literature method [73][74][75][76][77][78]. These observations prompted us to undertake the investigation of naphthofuran with oxadiazole and indole as second heterocyclic components.…”

Section: Biologically Active Naphthofuransmentioning

confidence: 99%

Synthesis, reactions and applications of naphthofurans: A review

Abdelwahab

Fekry

2021

Eur J Chem

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Considering the highly important biological and medicinal properties of naphthofurans, the synthesis of these heterocycles has attracted the interest of medicinal and organic chemists. This review aims to describe the different strategies developed so far for the synthesis of naphthofurans and their applications and the literature reports for the period of 2000 to early 2020. After a brief introduction of the types of naphthofurans and their biological activities, the different synthetic approaches such as chemical and photochemical, methods are described and organized on the basis of the catalysts and the other reagents employed in the syntheses. Some of the reactions have been applied successfully to the synthesis of biologically important compounds.

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“…All chemicals were purchased in the highest purity available. The four tetrahydroindeno [1,2-b]indole-9,10-diones 5a,b were synthesized according to previously reported methods [38,40,41] (detailed description of the synthetic pathway can be found in Supporting Information; Scheme S1). Compounds 5a,b and CX-4945 were dissolved at a concentration of 10 mM in dimethyl sulfoxide (DMSO).…”

Section: Chemical Synthesismentioning

confidence: 99%

4,5,7‐Trisubstituted indeno[1,2‐b]indole inhibits CK2 activity in tumor cells equivalent to CX‐4945 and shows strong anti‐migratory effects

et al. 2021

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Highly pleiotropic and constitutively active protein kinase CK2 is a key target in cancer therapy, but only one small-molecule inhibitor has reached clinical trials-CX-4945. In this study, we present the indeno[1,2-b]indole derivative 5-isopropyl-4-methoxy-7-methyl-5,6,7,8-tetrahydroindeno[1,2-b] indole-9,10-dione (5a-2) that decreased the intracellular CK2 activity in A431, A549, and LNCaP tumor cell lines analogous to CX-4945 (> 75% inhibition at 20 µM) and similarly blocked CK2-specific Akt phosphorylation in LNCaP cells. Cellular uptake analysis demonstrated higher intracellular concentrations of 5a-2 (408.3 nM) compared with . This finding clarifies the comparable effects of both compounds on the intracellular CK2 activity despite their different inhibitory potency in vitro [IC 50 = 25 nM (5a-2) and 3.7 nM (CX-4945)]. Examination of the effects of both CK2 inhibitors on cancer cells using live-cell imaging revealed notable differences. Whereas CX-4945 showed a stronger pro-apoptotic effect on tumor cells, 5a-2 was more effective in inhibiting tumor cell migration. Our results showed that 49% of intracellular CX-4945 was localized in the nuclear fraction, whereas 71% of 5a-2 was detectable in the cytoplasm. The different subcellular distribution, and thus the site of CK2 inhibition, provides a possible explanation for the different cellular effects. Our study indicates that investigating CK2 inhibition-mediated cellular effects in relation to the subcellular sites of CK2 inhibition may help to improve our understanding of the preferential roles of CK2 within different cancer cell compartments.Human protein kinase CK2 is a constitutively active serine/threonine kinase [1]. Today, the enzyme, which was first described in 1954 as 'casein kinase 2', is known to phosphorylate more than 500 substrates [2,3]. Together with an ubiquitous expression in eukaryotic cells [4], this high pleiotropy is the reason

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QSAR Model of Indeno[1,2-b]indole Derivatives and Identification of N-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-b]furan-3-carboxamide as a Potent CK2 Inhibitor

Cited by 12 publications

References 40 publications

Recent Advances in [3+2]-Cycloaddition-Enabled Cascade Reactions: Application to Synthesize Complex Organic Frameworks

Recent Advances in [3+2]-Cycloaddition-Enabled Cascade Reactions: Application to Synthesize Complex Organic Frameworks

Synthesis, reactions and applications of naphthofurans: A review

4,5,7‐Trisubstituted indeno[1,2‐b]indole inhibits CK2 activity in tumor cells equivalent to CX‐4945 and shows strong anti‐migratory effects

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